Most Antidepressants Could Be Ineffective, Unsafe for Young People

By staff

Oxford, UK—Are the vast majority of available antidepressants ineffective—and possibly unsafe—for children and adolescents? That’s what a new international review suggests.

The report, published in The Lancet, indicates that out of 14 antidepressant drugs, only fluoxetine was more effective at relieving the symptoms of depression than placebo. On the other hand, the study led by researchers from Oxford University in the United Kingdom and The First Affiliated Hospital of Chongqing Medical University in China suggested that venlafaxine was linked with an increased risk of engaging in suicidal thoughts and attempts, compared with placebo and five other antidepressants.

Study authors caution that they were unable to quantify some of the harmful effects because of the small number and poor design of clinical trials assessing the antidepressants in youth, as well as the selective reporting of findings in published trials and clinical study reports.

“The balance of risks and benefits of antidepressants for the treatment of major depression does not seem to offer a clear advantage in children and teenagers, with probably only the exception of fluoxetine,” explained co-author Peng Xie, MD of The First Affiliated Hospital of Chongqing Medical University. “We recommend that children and adolescents taking antidepressants should be monitored closely, regardless of the antidepressant chosen, particularly at the beginning of treatment.”

For the study, researchers did a systematic review and network meta-analysis of all published and unpublished randomized trials comparing the effects of 14 antidepressants in young people with major depression up to the end of May 2015. They ranked antidepressants by efficacy (change in depressive symptoms and response to treatment), tolerability (discontinuation due to adverse events), acceptability (discontinuation due to any cause), and associated serious harms (i.e., suicidal thoughts and attempts). They took into account the quality of included studies (Cochrane risk of bias) and also assessed the overall quality of the retrieved evidence (GRADE).

Results ultimately were based on analysis of 34 trials involving 5,260 participants, average age 9 to 18 years, and indicate that benefits outweighed the risks in terms of efficacy and tolerability only for fluoxetine. The study notes that nortriptyline was less efficacious than seven other antidepressants and placebo, while imipramine, venlafaxine, and duloxetine had the worst profile of tolerability, leading to significantly more discontinuations than placebo.

Venlafaxine was linked with an increased risk of engaging in suicidal thoughts or attempts compared with placebo and five other antidepressants, according to the report.

Overall quality of evidence for primary outcomes was rated as very low for most comparisons, which restricts the implications of the results for clinical practice, according to the authors. Part of the problem is the unavailability of raw data.

“Without access to individual-level data it is difficult to get accurate effect estimates, and we can't be completely confident about the accuracy of the information contained in published and unpublished trials,” explained lead author Andrea Cipriani, PhD, of the University of Oxford in the UK. “It has been widely argued that there needs to be a transformation of existing scientific culture to one where responsible data sharing should be the norm.”